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ID: ALA1759994

Journal: Bioorg Med Chem Lett

Title: The discovery and synthesis of potent zwitterionic inhibitors of renin.

Authors: Aspiotis R, Chen A, Cauchon E, Dubé D, Falgueyret JP, Gagné S, Gallant M, Grimm EL, Houle R, Juteau H, Lacombe P, Laliberté S, Lévesque JF, MacDonald D, McKay D, Percival MD, Roy P, Soisson SM, Wu T.

Abstract: The incorporation of a carboxylic acid within in a series of 3-amido-4-aryl substituted piperidines (represented by general structure 32) led to the discovery of potent, zwitterionic, renin inhibitors with improved off-target profiles (CYP3A4 time-dependent inhibition and hERG affinity) relative to analogous non-zwitterionic inhibitors of the past (i.e., 3). Strategies to address the oral absorption of these zwitterions are also discussed within.

CiteXplore: 21429746

DOI: 10.1016/j.bmcl.2011.02.067